1. Field of the Invention
The present invention relates to a method of preparing an antithrombogenic medical material
2. Description of the Prior Art
Many medical materials used in the treatment of cardiovascular diseases are required to possess antithrombogenic properties. For instance, in the case of artificial blood-vessels, artificial valves, artificial hearts, and parts of artificial lung devices, if the surfaces coming into contact with blood possess blood coagulating properties, serious problems such as thrombosis may arise. In order to alleviate such problems, a variety of antithrombogenic medical materials consisting of synthetic polymer materials such as a polyurethane have been developed so far. These materials, however, do not always possess sufficient compatibility with endothelial cells and other cells of the living tissues, and therefore with these materials it was difficult to obtain satisfactory antithrombogenic properties.
Collagen is a protein, which is present in connective tissues and basement membranes of animal and is highly compatible with the cells Since collagen has no antithrombogenic property in itself, it is necessary to provide collagen with antithrombogenic properties in order to make the collagen usable as a medical material coming into contact with blood A simple and safe way of providing collagen with antithrombogenic properties is to combine heparin with the collagen through a protamine, in which the protamine is fixed to the collagen through a cross-linking agent For instance, Japanese Patent Application Laid Open No. 58-180162 discloses an antithrombogenic medical material consisting of a heparinized collagen in which heparin is attached to a protamine which is fixed to a collagen of animal origin through glutaraldehyde as a cross-linking agent.
The heparin in the heparinized collagen forms an ionic-bond with protamine and is released slowly in the living body to prevent blood from coagulating. It is further noted that since endothelial cells grow on the collagen base, antithrombogenic properties are maintained by the endothelial cells after the heparin is entirely released
Since, however, glutaraldehyde is used as a cross-linking agent for fixing a protamine to the collagen, the resulting heparinized collagen will have a decreased flexibility and form constrictions or cracks when it is bent to a small radius of curvature. It is also likely that the glutaraldehyde discolors the heparinized collagen to brown, and that the glutaraldehyde is polymerized and released slowly as a polymer under some conditions in the living body, which may cause toxicity for a long period of time.